Targeting AR-positive breast cancer cells via drug repurposing approach.

Androgen Receptor (AR) is overexpressed in almost all the molecular subtypes of breast cancer. Besides aiding the tumorigenic environment of cancer by abnormal cell proliferation, AR also takes part in promoting cancer signaling pathways, thereby promoting aggressiveness. In this study, AR was selected as the target protein in breast cancer cells. Following this, a library of 1293 FDA-approved drugs was screened via molecular docking, MD simulation, and MMPBSA binding energy. Amongst the library of compounds, Adapalene exhibited the least binding energy of (-10.2 kCal/mol) in comparison to that of the chosen reference compound, Nilutamide (-8.6 kCal/mol). Furthermore, the in vitro efficacy of Adapalene was also determined in two different breast cancer cell lines such as MCF7 (AR-positive/ER-positive) and MDA-MB-231 (AR negative/TNBC). Initially, the cell viability assay (MTT) was performed, which endowed us with a lesser IC50 value of Adapalene in comparison to Nilutamide in both cell lines. The IC50 of Adapalene was found to be 12 µM and 39.4 µM in MCF7 and MDA-MB-231 cells, respectively. Furthermore, Adapalene also induced cellular ROS and apoptosis by 3.5-fold and 26.58% in MCF7 cells. However, the overall effect of Adapalene was significantly lower in the case of MDA-MB-231 cell lines, which could be attributed to its inherent nature of the absence of hormone receptors. Conclusively, Adapalene possesses greater therapeutic efficacy in comparison to the control drug, thereby hinting towards the potential use of Adapalene in the treatment of AR-positive breast cancer.

Emerging Promise of Phytochemicals in Ameliorating Neurological Disorders.

BACKGROUND: The field of medicine and synthetic drug development have advanced rapidly over the past few decades. However, research on alternative medicine such as phytochemicals cannot be ignored. The main reason for prominent curiosity about phytochemicals stems from the belief that usage of natural compounds is safer and has lesser detrimental side effects. OBJECTIVE: The aim of the present review was to discuss in detail with several phytochemicals that have been studied or are being studied in the context of various neurological disorders including depression, Alzheimer's disease, Huntington's disease and even neuroinflammatory disorders such as encephalitis. METHODS: The potential role of phytochemicals in the treatment or management of symptoms associated with neurological disorders have been included in this article. All data included in this paper has been pooled from various databases including Google Scholar, PubMed, Science Direct, Springer and Wiley Online Library. RESULTS: Phytochemicals have been widely studied for their therapeutic properties associated with neurological disorders. Using various experimental techniques for both in vivo and in vitro experiments, studies have shown that phytochemicals do have antioxidant, anti-inflammatory and neuroprotective activities which play major roles in the treatment of neurological diseases. CONCLUSION: Even though there has been compelling evidence of the therapeutic role of phytochemicals, further research is still required to evaluate the safety and efficacy of these medicines. Using previously published papers as foundation for additional research such as preclinical studies and clinical trials, phytochemicals can become a safer alternative to synthetic drugs for treating a spectrum of neurological diseases.